Caffeine attenuates liver fibrosis via defective adhesion of hepatic stellate cells in cirrhotic model.

BACKGROUND AND AIM: Several epidemiological studies have shown that coffee intake attenuates the progression of liver fibrosis; however, the mechanism is unclear. AIMS: We investigated the direct effects of caffeine on hepatic stellate cells (HSCs) and assessed whether caffeine attenuated intrahepatic fibrosis in rat model of liver cirrhosis. METHODS: Human hepatic stellate cell line, an immortalized human HSCs line, was used in in vitro assay system. Cell migration and proliferation were assessed in presence of various caffeine concentrations (0, 1, 5, and 10 mmol), and levels of procollagen type Ic and α-smooth muscle actin (α-SMA) were measured by Western blot. Severity of liver inflammation and fibrosis were compared between thioacetamide-treated rats with and without caffeine supplementation. RESULTS: Caffeine increased HSCs apoptosis and intracellular F-actin and cyclic adenosine monophosphate expression. Caffeine also inhibited procollagen type Ic and α-SMA expression in a dose- and time-dependent manner. In rat model, caffeine decreased periportal inflammation, levels of inflammatory cells (1.4 ± 0.52 vs 2.6 ± 0.46, P < 0.05), and fibrosis (2.1 ± 0.35 vs 2.9 ± 0.84, P < 0.05). Transforming growth factor-ß and α-SMA expressions were also reduced by caffeine. CONCLUSION: Caffeine attenuates the progression of liver fibrosis by inhibiting HSCs adhesion and activation.

The Differences in Prevalence and Sociodemographic Characteristics of Irritable Bowel Syndrome According to Rome II and Rome III.

BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is one of the most frequently observed disorders by primary care and practitioners. The aim of this study was to estimate the prevalence of IBS using the Rome II and III criteria in the general Korean population and also to compare sociodemographic differences between subjects diagnosed by these criteria. METHODS: Telephone interview surveys were performed with a total of 1,009 individuals in Korea, 15 years of age or older. The questionnaire, based on the Rome II and III criteria, was validated. RESULTS: Among the 1,009 subjects, the prevalence of IBS was 8.0% under the Rome II criteria (81 subjects; 6.4%, male; 9.6%, female), and 9.0% (91 subjects; 7.0%, male; 11.0%, female) under the Rome III criteria. The accordance rate of Rome II and III was 73.5%. Both groups showed highest frequency in the age of 30s (13.9% vs. 15.3% respectively). Female subjects showed a higher prevalence than male subjects under Rome III (91 subjects; 11.0% in female, 7.0% in male; p < 0.05), but not under Rome II criteria. Many patients older than 50 years were added when analyzed under the Rome III criteria, but not under the Rome II criteria (p = 0.017). CONCLUSIONS: The Rome III criteria were less restrictive and showed good agreement with the Rome II criteria. The prevalence of IBS was increased in young women.

[A case of nodular regenerative hyperplasia of liver that mimicked primary biliary cirrhosis].

Nodular regenerative hyperplasia (NRH) of the liver is a rare disease that is characterized by multiple regenerative nodules in the hepatic parenchyma without fibrosis. The exact pathogenesis of NRH has not been established, but it's been suggested that obliteration of portal veins may initiate the nodular transformation. It is also known that this disease is associated with autoimmune disease, myeloproliferative disease, lymphoproliferative disease, primary biliary cirrhosis, and some chemotherapy agents. The patients with NRH are usually asymptomatic, yet if they have symptoms, the most common clinical manifestations are those of portal hypertension, including splenomegaly and esophageal varices with or without bleeding. We report a case of nodular regenerative hyperplasia that presented with clinical manifestations similar to those of primary biliary cirrhosis.

[The significance of urine sodium measurement after furosemide administration in diuretics-unresponsive patients with liver cirrhosis].

BACKGROUND/AIMS: The diagnosis of refractory ascites means a poor prognosis for patients with liver cirrhosis. The definition of refractory ascites has already been established, but using the dosage of diuretics that correlates with the definition of refractory ascites in an out-patient department will lower the compliance of the patient, as well as causing serious complications, such as hepatic encephalopathy and hyponatremia, as the dosage of diuretics is increased. Due to this fact, it is very difficult to apply this definition of refractory ascites to patients in a domestic out-patient department. In this study, in situations where there are difficulties in applying the diuretics dosage according to definition of refractory ascites, we tried to find out whether measuring the value of urine sodium after the administration of intravenous furosemide can be the standard in early differentiation of the response to diuretics treatment. METHODS: We reviewed 16 cases of liver cirrhosis with ascites and classified them into two groups by the response to diuretics. The diuretics-responsive ascites group was 8 cases and the diuretics-unresponsive ascites group consisted of 8 cases. After admission, we examined the patients' CBC, biochemical liver function test, spot urine sodium, and 24 hour creatinine clearance. After the beginning of the experiment, all diuretic therapy was stopped for 3 days. Daily we examined the patients' CBC, biochemical liver function test, and in the 3rd experiment day, we measured 24-hour urine volume and sodium. In the 4th experiment day, after sampling for ADH, plasma renin activity and plasma aldosterone level, we administrated the furosemide 80 mg I.V, and measured the amount of 8 hour urine volume and sodium. RESULTS: The plasma aldosterone level was significantly higher in the diuretics- unresponsive ascites group than in the diuretics-responsive ascites group. In the 4th experiment day, the amount of urine volume and sodium was very significantly lower in the diuretics-unresponsive ascites group than in the diuretics-responsive ascites group (1297.5 +/-80.9 vs 2003.7 +/-114.6 ml, p<0.005, 77.3 +/-8.2 vs 211.8 +/-12.6 mEq, p<0.001). CONCLUSIONS: In out-patient departments, the measurement of urine sodium 8 hours after administrating 80 mg of intravenous furosemide, will help in differentiating ascites patients with lower treatment response to diuretics.

[Five-year follow-up of clinical and laboratory data of early liver cirrhosis patients confirmed by liver biopsy].

BACKGROUND/AIMS: It is important to evaluate the general status of the liver including the structural and inflammatory aspects, as well as the functional aspects, in order to determine a patient's treatment modality and prognosis. METHODS: 55 Child-Pugh class A liver cirrhosis patients confirmed by liver biopsy have been categorized into 4 groups based on the shunt index and p-value(Y= 3.3431-0.8160 ALT/AST ratio-0.0343 X prothrombin time+2.6963 X shunt index, p = e(y)/(e(y)+1)), which was obtained by Thallium- 201 scan; group I - shunt index less than 0.3 and p-value less than 0.7; group II - shunt index less than 0.3 and p-value more than 0.7; group III - shunt index more than 0.3 and p-value less than 0.7; and group IV - shunt index more than 0.3 and p-value more than 0.7. Statistical analyses used were ANOVA, paired t-test, and Chi-square test. RESULTS: 1. The laboratory data after a 5-year follow-up also showed a significant difference between four groups. 2. In group IV, the Child-Pugh class after 5 years worsened, and complications of liver cirrhosis such as esophageal varix, ascites, and hepatic encephalopathy occurred more frequently. 3. In group II, the laboratory data after a 5-year follow-up indicated some improvement. CONCLUSION: It can be seen that even early in patients with initially the same cirrhosis, the course of the illness can progress to a variety of different situations. The measurement of shunt index and the p-value of cirrhosis will be more helpful in the follow-up evaluation and predicting its prognostic index in liver cirrhosis patients.